# Differences in enteric neuronal density in the NSE-Noggin mouse model across institutes

## TL;DR

This study found that NSE-Noggin mice did not show increased enteric neuronal density in the colon, contrary to previous reports, and explores possible reasons for the discrepancy.

## Contribution

The study highlights inconsistencies in the NSE-Noggin mouse model's hyperinnervated phenotype across different research settings.

## Key findings

- NSE-Noggin mice did not show a higher total number of enteric neurons compared to wild types.
- The proportion of specific enteric neuron subtypes was also unchanged in NSE-Noggin mice.
- Possible explanations for the discrepancy include study design and environmental factors like microbiota.

## Abstract

The enteric nervous system (ENS) is a large and complex part of the peripheral nervous system, and it is vital for gut homeostasis. To study the ENS, different hyper- and hypo-innervated model systems have been developed. The NSE-Noggin mouse model was described as one of the few models with a higher enteric neuronal density in the colon. However, in our hands NSE-Noggin mice did not present with a hyperganglionic phenotype. NSE-Noggin mice were phenotyped based on fur appearance, genotyped and DNA sequenced to demonstrate transgene and intact NSE-Noggin-IRES-EGFP construct presence, and RNA expression of Noggin was shown to be upregulated. Positive EGFP staining in the plexus of NSE-Noggin mice also confirmed Noggin protein expression. Myenteric plexus preparations of the colon were examined to quantify both the overall density of enteric neurons and the proportions of enteric neurons expressing specific subtype markers. The total number of enteric neurons in the colonic myenteric plexus of transgenic mice did not differ significantly from wild types, nor did the proportion of calbindin, calretinin, or serotonin immunoreactive myenteric neurons. Possible reasons as to why the hyperinnervated phenotype could not be observed in contrast with original studies using this mouse model are discussed, including study design, influence of microbiota, and other environmental variables.